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Interpretations of antemortem and perimortem trauma are complicated when dealing with cases involving extreme exposure to fire. This investigation attempts to discern the signatures of perimortem trauma from heat related trauma. Femora of domestic pig, sus scrofa, with minimal soft tissue and articulated patellae were subjected to varying traumatic forces. Skeletal elements were impacted with blunt and sharp forces, cut with varying instruments, subjected to torsional forces or shot. Bones were burned in various situations in conjunction with Knox County Rural/Metro Fire Department training exercises conducted in Knox County, Tennessee. Following recovery, fragments were subjected to radiographic, macroscopic, and microscopic analyses. Skeletal elements were reconstructed to permit accurate comparison with pre-fire visual records. In addition, fracture surfaces were examined under both transmitted light and scanning electron microscopy in an attempt to discern surface signatures of the causal fracture (trauma, heat, or situational). Results indicate that signatures of sharp force trauma remain evident following incineration. Furthermore, radiopaque spatter was not observed in any shot specimen. However, these initial findings suggest that the interpretation of blunt force and torsional trauma requires a rigorous examination and comparison of fracture patterns in conjunction with surface morphology.

1 Intestinal xenobiotic transporters are a signi®cant barrier to the absorption of many orally administered drugs. P-glycoprotein (PGP) is the best known, but several others, including members of the multidrug resistance-associated protein (MRP) family, are also expressed. De®nitive information on their precise e ect on intestinal drug permeability is scarce due to a lack of speci®c inhibitors and the di culty of studying non-PGP activity in the presence of high PGP expression. 2 We have investigated the in vitro use of intestinal tissues from PGP knockout (mdr1a (7/7)) mice as a tool for dissecting the mechanisms of intestinal drug e ux. The permeability characteristics of digoxin (DIG), paclitaxel (TAX) and etoposide (ETOP) were measured in ileum from mdr1a (7/7) and wild-type (FVB) mice mounted in Ussing chambers. 3 DIG and TAX exhibited marked e ux across FVB tissues (B-A : A-B apparent permeability (P app ) ratio 10 and 17 respectively) which was absent in mdr1a (7/7) tissues, con®rming that PGP is the sole route of intestinal e ux for these compounds. The A-B P app of both compounds was 3 ± 5 fold higher in mdr1a (7/7) than in FVB. 4 Polarized transport of ETOP in FVB tissues was reduced but not abolished in mdr1a (7/7) tissues. Residual ETOP e ux in mdr1a (7/7) tissues was abolished by the MRP inhibitor MK571, indicating involvement of both PGP and MRP. 5 MK571 abolished calcein e ux in mdr1a (7/7) tissues, while quinidine had no parallel e ect in FVB tissues, suggesting involvement of MRP but not PGP. 6 Tissues from mdr1a (7/7) mice provide a novel approach for investigating the in¯uence of PGP ablation on intestinal permeability and for resolving PGP and non-PGP mechanisms that modulate drug permeability.

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4–12 years) and 61 adults (18–37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5–10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies.

Chloroquine bioavailability in healthy males was examined following oral coadministration of 600 mg with three common Sudanese beverages, Aradaib (Tamarindus indica), Karkadi (Hibiscus sabdarifa) and Lemon (Citrus limetta) and drinking water. The tablets and beverages were taken on an empty stomach after an overnight fast. The plasma chloroquine concentrations were measured by HPLC. The extent and rate of chloroquine bioavailability were described by the area under the plasma concentrations versus time curve (AUC), the peak plasma concentration (Cmax) and with the time to reach Cmax (Tmax), respectively. The mean (+/- S.E.) AUC values after administration with water (control) and Aradaib, Karkadi and Lemon, respectively, were 7.52 +/- 0.87, 2.60 +/- 0.24, 2.16 +/- 0.30 and 2.41 +/- 0.29 mg.h/L. The corresponding mean Cmax values were 553 +/- 17.8, 184 +/- 21.3, 148 +/- 14.1 and 210 +/- 17.4 mg/L and the corresponding Tmax values were 3.0 +/- 1.0, 3.2 +/- 1.2, 2.6 +/- 0.8 and 2.5 +/- 1.0 h. The results indicate a statistically significant reduction in the AUC and Cmax of chloroquine as a result of a coadministration with each of the three beverages. A parallel reduction in the drugs antimalarial efficacy might be expected.

Predicting oral bioavailability (F oral The OrBiTo database was found to be largely representative of previously published datasets.)43 of the APIs were found to satisfy the minimum inclusion criteria for the simulation exercise, and many of these have significant gaps of other key parameters, which could potentially impact the interpretability of the simulation outcome. However, the OrBiTo simulation exercise represents a unique opportunity to perform a large-scale evaluation of the PBPK approach to predicting oral biopharmaceutics. Keywords:Physiologically-based pharmacokinetics (PBPK); modelling and simulation (M&S); absorption; oral bioavailability (F oral ); biopharmaceutics; drug database

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LVOT eccentricity and discordant sizing predict PVL after S3 TAVI. Further studies are needed to understand their mechanism and significance.